In-situ hybridization histochemistry was used to measure corticotrophin-releasing factor mRNA and proenkephalin A mRNA in the paraventricular nucleus (PVN), and pro-opiomelanocortin (POMC) mRNA in the anterior pituitary of the rat. Levels of message were determined at 1, 2, 4 and 8 h after exposure to a variety of physical and psychological stresses. Corticotrophin-releasing factor mRNA in the PVN and POMC mRNA in the anterior pituitary increased in response to i.p. hypertonic saline, restraint and swim stress but not to cold stress. Proenkephalin A mRNA was raised only in response to the physical stress of i.p. injection of hypertonic saline. These results suggest that different afferent pathways and hypothalamic neurotransmitters may be involved in mediating the hypothalamic response to different physical and psychological stresses.